Common ECG Finding Confers Greater Mortality Risk than Diabetes, Coronary Artery Disease

The presence of left ventricular conduction disease (LVCD), regardless of the length of conduction delay, is more strongly associated with all-cause and cardiovascular mortality than coronary artery disease, LV hypertrophy or diabetes, according to an analysis of the PRECISION trial recently published in the American Journal of Cardiology (2019 Jul 15 [Epub ahead of print]).

“We have long established that delayed left ventricular conduction in the form of left bundle branch block [LBBB] confers markedly increased risk for cardiovascular and overall mortality in patients,” says the study’s corresponding and senior author, Daniel Cantillon, MD, of Cleveland Clinic’s Section of Electrophysiology and Pacing. “Our analysis makes a strong case for recognizing any type of delayed LV conduction among well-recognized cardiovascular risk factors, and thus changing how we think about overall cardiovascular health.”

New subclassification scheme for intraventricular conduction delay

This post hoc analysis included 22,607 (94%) of the randomized, double-blind, multicenter PRECISION trial’s 24,081 patients. PRECISION found in 2016 that celecoxib does not confer excess cardiovascular risk and is associated with fewer cardiovascular adverse events compared with both naproxen and ibuprofen in patients with rheumatoid arthritis or osteoarthritis. Patients enrolled underwent a baseline 12-lead ECG. The Cleveland Clinic Coordinating Center for Clinical Research (C5Research) adjudicated all-cause and cardiovascular mortality as well as heart failure (HF) hospitalizations and ECG results.

The present study categorized QRS duration as narrow (≤ 100 ms) or prolonged (> 100 ms), with prolongation further classified into LBBB, right bundle branch block (RBBB) and intraventricular conduction delay (IVCD). LBBB and RBBB were identified according to standard definitions (QRS duration > 120 ms).

IVCD was defined overall as QRS 101 to 120 ms irrespective of morphology, or as QRS > 120 ms not identifiable as BBB. The researchers devised a first-of-kind subclassification scheme for IVCD. IVCD with LBBB-predominant features (L-IVCD) required the following ECG findings: (1) lead V1 net negative; (2) lead V1 without terminal positivity; and (3) lead I net positive. Subjects without these findings were categorized as non-LBBB-predominant (O-IVCD).

Average follow-up was 34 ± 13 months. Mean age was 63 years, and 64% of patients were female. Twenty-three percent had established cardiovascular disease, and arthritis type was adjusted for in multivariate analysis. Outcomes measured were all-cause and cardiovascular mortality, with HF hospitalization a secondary outcome.

Dyssynchrony as a diagnostic parameter

Of the overall sample, 1,240 patients (5.6%) had QRS prolongation and broke down as follows:

• 766 (3.4%) had RBBB
• 313 (1.4%) had LBBB
• 161 (0.7%) had IVCD, with 95 (0.4%) subclassified as L-IVCD

After multivariable adjustment, analysis showed that LBBB and L-IVCD were both associated with an increased hazard ratio (HR) for all-cause and cardiovascular mortality, as follows:

• HR for all-cause mortality:
  LBBB, 2.3 [95% CI, 1.4-3.8] (P = 0.001)
  L-IVCD, 4.0 [95% CI, 2.1-7.9] (P < 0.001)
• HR for cardiovascular mortality:
  LBBB, 3.6 [95% CI, 2.0-6.5] (P < 0.001)
  L-IVCD, 3.6 [95% CI, 1.3-9.7] (P = 0.001)

Overall LCVD was associated with greater all-cause mortality (adjusted HR = 2.8 [95% CI, 1.8-4.2], P < 0.001) and cardiovascular mortality (adjusted HR = 3.6 [2.2-6.1], P < 0.001) than were observed risks of LV hypertrophy, diabetes and coronary artery disease. Patients’ cardiovascular disease status and QRS duration did not affect results.

The researchers’ IVCD classification scheme also proved valid for mortality stratification, although it needs further validation in additional cohorts. Patients with O-IVCD mirrored those with RBBB and narrow QRS, and L-IVCD survival tracked with LBBB. “What is striking about these findings is that it didn’t matter how long QRS was prolonged,” notes Oussama Wazni, MD, Section Head of Electrophysiology and Pacing. “It was the prolongation itself — not necessarily its length — that conferred increased mortality risk.”

“Delays in left ventricular conduction are fairly common ECG findings,” says Steven Nissen, MD, Chief Academic Officer of Cleveland Clinic’s Miller Family Heart & Vascular Institute and principal investigator of the overall PRECISION trial. “Putting these delays in the same risk category as diabetes and coronary artery disease is a significant change in practice and allows us to identify and manage previously undetected risk in our patients.”